rs11202607
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1
The NM_000314.8(PTEN):c.*2185C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 219,966 control chromosomes in the GnomAD database, including 589 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.068 ( 419 hom., cov: 31)
Exomes 𝑓: 0.071 ( 170 hom. )
Consequence
PTEN
NM_000314.8 3_prime_UTR
NM_000314.8 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.281
Genes affected
PTEN (HGNC:9588): (phosphatase and tensin homolog) This gene was identified as a tumor suppressor that is mutated in a large number of cancers at high frequency. The protein encoded by this gene is a phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase. It contains a tensin like domain as well as a catalytic domain similar to that of the dual specificity protein tyrosine phosphatases. Unlike most of the protein tyrosine phosphatases, this protein preferentially dephosphorylates phosphoinositide substrates. It negatively regulates intracellular levels of phosphatidylinositol-3,4,5-trisphosphate in cells and functions as a tumor suppressor by negatively regulating AKT/PKB signaling pathway. The use of a non-canonical (CUG) upstream initiation site produces a longer isoform that initiates translation with a leucine, and is thought to be preferentially associated with the mitochondrial inner membrane. This longer isoform may help regulate energy metabolism in the mitochondria. A pseudogene of this gene is found on chromosome 9. Alternative splicing and the use of multiple translation start codons results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 10-87967657-C-T is Benign according to our data. Variant chr10-87967657-C-T is described in ClinVar as [Benign]. Clinvar id is 301483.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.128 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTEN | NM_000314.8 | c.*2185C>T | 3_prime_UTR_variant | 9/9 | ENST00000371953.8 | ||
PTEN | NM_001304717.5 | c.*2185C>T | 3_prime_UTR_variant | 10/10 | |||
PTEN | NM_001304718.2 | c.*2185C>T | 3_prime_UTR_variant | 9/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTEN | ENST00000371953.8 | c.*2185C>T | 3_prime_UTR_variant | 9/9 | 1 | NM_000314.8 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0681 AC: 10326AN: 151706Hom.: 418 Cov.: 31
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GnomAD4 exome AF: 0.0707 AC: 4820AN: 68142Hom.: 170 Cov.: 0 AF XY: 0.0718 AC XY: 2268AN XY: 31572
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GnomAD4 genome ? AF: 0.0680 AC: 10330AN: 151824Hom.: 419 Cov.: 31 AF XY: 0.0687 AC XY: 5097AN XY: 74218
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
PTEN hamartoma tumor syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at